Cell Rep:利用CRISPR技术发现寨卡病毒和登革热病毒弱点

2016-06-22 佚名 生物谷

\在一项新的研究中,来自美国马萨诸塞大学医学院的研究人员开展首次利用CRISPR/Cas9筛选,发现寨卡病毒和登革热病毒复制所需要的人蛋白。这项研究揭示出的新进展有可能被用来阻止寨卡病毒、登革热病毒和其他新发的病毒感染。相关研究结果于2016年6月21日在线发表在Cell Reports期刊上,论文标题为“Identification of Zika Virus and Dengue Virus

\在一项新的研究中,来自美国马萨诸塞大学医学院的研究人员开展首次利用CRISPR/Cas9筛选,发现寨卡病毒和登革热病毒复制所需要的人蛋白。这项研究揭示出的新进展有可能被用来阻止寨卡病毒、登革热病毒和其他新发的病毒感染。相关研究结果于2016年6月21日在线发表在Cell Reports期刊上,论文标题为“Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics”。论文通信作者为马萨诸塞大学医学院微生物学与生理学系统助理教授Abraham Brass博士。
 
寨卡病毒首先是从非洲的一只感染的猕猴中分离出来的。2007年,它突然出现在密克罗尼西亚,随后扩散到东南亚。2015年5月,寨卡病毒在巴西被鉴定出。随着它在中、南美洲快速扩散,它被视为一种严重的健康威胁,这是因为它能够导致新生儿小头畸形(microcephaly),还能导致儿童和成年人患上格林-巴利综合征(Guillain-Barre syndrome)。尽管寨卡病毒感染被世界卫生组织(WHO)宣布为一种突发公共卫生事件,但是当前没有治疗它的方法。阻止寨卡病毒感染的最好方法是限制对携带这种病毒的蚊子的潜在接触。
 
鉴于寨卡病毒和登革热病毒自身只编码几种蛋白,它们必需征用宿主细胞的资源和蛋白来进行生长和复制。一些用于抵抗HIV和HCV的抗病毒疗法通过破坏病毒利用这些资源的能力来发挥疗效的。利用这种抗病毒方法治疗寨卡病毒和登革热病毒感染的第一步就是从2万多种人蛋白中找出这些病毒进行复制所需的蛋白。
 
Brass说,“这些病毒对人蛋白的依赖代表着可能潜在地被用来预防或阻止感染的弱点。正如任何一种敌人一样,我们对这些病毒如何发挥功能和复制了解得越多,结果就会越好。”
 
在这项研究中,Brass和他的同事们Timothy F. Kowalik博士、Sharone Green博士都是黄病毒专家,其中黄病毒是由蚊子传播的病毒家族,包括寨卡病毒、黄热病毒、登革热病毒和西尼罗河病毒。他们开发出一套功能强大的工具,包括RNAi、CRISPR技术、病毒进化分析和小鼠模型,来分析这些病毒入侵者如何利用宿主细胞蛋白进行复制。
 
利用开发出的RNAi和CRISPR/Cas9筛选技术, 研究人员首先每次基因敲除或剔除人基因组中的一种蛋白编码基因,然后观察寨卡病毒或登革热病毒如何生长。
 
基于此,Brass和同事们鉴定出几种在寨卡病毒和登革热病毒复制中发挥着关键作用的宿主蛋白。其中一种就是AXL蛋白,这两种病毒利用它侵入宿主细胞。他们也鉴定出内质网膜蛋白复合物(EMC)在这两种病毒早期感染中发挥着至关重要的作用。总之,这些发现代表着潜在的治疗靶标,可能有助人们治疗和预防感染。下一步就是开发靶向这些蛋白抑制寨卡病毒和登革热病毒感染的疗法。

原始出处

George Savidis5, William M. McDougall5, Paul Meraner5, Jill M. Perreira, Jocelyn M. Portmann, Gaia Trincucci, Sinu P. John, Aaron M. Aker, Nicholas Renzette, Douglas R. Robbins, Zhiru Guo, Sharone Green, Timothy F. Kowalik, Abraham L. Brass.Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics.Cell Rep.2016

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    2016-11-23 维他命
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    2016-06-24 yuandd
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